In the proposed studies will investigate those factors involved in the control of utero-placental circulation. Utilizing chronic sheep preparations, methods have been developed which permit serial blood sampling from and drug administration to either the mother and/or fetus, and the direct measurement of uterine blood flow and its distribution. Areas of interest include the origin and vascular effects of endogenous steroids and the circulatory effects of pharmacologic agents employed in pregnancy. Investigation of the endogenous control of utero-placental circulation will provide a description of the role of placental circulation in fetal well-being, insight into fetal pathophysiology, and information about naturally occurring changes in utero-placental blood flow during pregnancy and parturition. Of particular interest is the correlation between the measurement of uterine blood flow, using the above methods, and the quantification of placental function determined by the rate of placental utilization of maternal plasma prehormones. This requires definition of the origin and physiology of estrogen in the sheep and will provide an indirect measurement of placental perfusion through evaluation of the placental clearance of estrogen precursors. These data also will provide information about endocrine events preceding and following parturition. By virtue of the methodology employed, alterations in cardiac output and regional blood flows can be studied, providing further information about the normal cardiovascular physiology of pregnancy and its aberrations.